Filed Pursuant to Rule 433 of the Securities Act of 1933 Issuer Free Writing Prospectus dated October 15, 2021 Relating to the Preliminary Prospectus dated October 15, 2021 Registration Statement File No. 333-256572 context therapeutics Advancing Medicines For Female Cancers Context Therapeutics Inc.Filed Pursuant to Rule 433 of the Securities Act of 1933 Issuer Free Writing Prospectus dated October 15, 2021 Relating to the Preliminary Prospectus dated October 15, 2021 Registration Statement File No. 333-256572 context therapeutics Advancing Medicines For Female Cancers Context Therapeutics Inc.
Forward Looking Statement Except for statements of historical fact, any information contained in These forward-looking statements are subject to a number of risks, this presentation may be a forward-looking statement that reflects uncertainties and assumptions, including those described under the the Company’s current views about future events and are subject to heading “Risk Factors” in documents the Company has filed with the risks, uncertainties, assumptions and changes in circumstances that SEC. These forward-looking statements speak only as of the date of may cause events or the Company’s actual activities or results to this presentation and the Company undertakes no obligation to differ significantly from those expressed in any forward-looking revise or update any forward-looking statements to reflect events or statement. In some cases, you can identify forward-looking circumstances after the date hereof. statements by terminology such as “may”, “will”, “should”, “plan”, “predict”, “expect,” “estimate,” “anticipate,” “intend,” “goal,” “strategy,” Certain information contained in this presentation may be derived “believe,” “could”, “would”, “potential”, “project”, “continue” and from information provided by industry sources. The Company similar expressions and variations thereof. believes such information is accurate and that the sources from which it has been obtained are reliable. However, the Company Forward-looking statements may include statements regarding the cannot guarantee the accuracy of, and has not independently Company’s business strategy, cash flows and funding status, verified, such information. potential growth opportunities, clinical development activities, the timing and results of preclinical research, clinical trials and potential Trademarks: The trademarks included herein are the property of the regulatory approval and commercialization of product candidates. owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, the Company cannot guarantee future events, results, actions, levels of activity, performance or achievements. 2 Nasdaq: CNTXForward Looking Statement Except for statements of historical fact, any information contained in These forward-looking statements are subject to a number of risks, this presentation may be a forward-looking statement that reflects uncertainties and assumptions, including those described under the the Company’s current views about future events and are subject to heading “Risk Factors” in documents the Company has filed with the risks, uncertainties, assumptions and changes in circumstances that SEC. These forward-looking statements speak only as of the date of may cause events or the Company’s actual activities or results to this presentation and the Company undertakes no obligation to differ significantly from those expressed in any forward-looking revise or update any forward-looking statements to reflect events or statement. In some cases, you can identify forward-looking circumstances after the date hereof. statements by terminology such as “may”, “will”, “should”, “plan”, “predict”, “expect,” “estimate,” “anticipate,” “intend,” “goal,” “strategy,” Certain information contained in this presentation may be derived “believe,” “could”, “would”, “potential”, “project”, “continue” and from information provided by industry sources. The Company similar expressions and variations thereof. believes such information is accurate and that the sources from which it has been obtained are reliable. However, the Company Forward-looking statements may include statements regarding the cannot guarantee the accuracy of, and has not independently Company’s business strategy, cash flows and funding status, verified, such information. potential growth opportunities, clinical development activities, the timing and results of preclinical research, clinical trials and potential Trademarks: The trademarks included herein are the property of the regulatory approval and commercialization of product candidates. owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, the Company cannot guarantee future events, results, actions, levels of activity, performance or achievements. 2 Nasdaq: CNTX
Free Writing Prospectus This Presentation is not an offer to sell, and is not seeking an This presentation shall not constitute an offer to sell or the offer to buy, any securities of Context Therapeutics Inc. (the solicitation of an offer to buy these securities, nor shall there be Company , or we, us, or our ). The Company's securities any sale of these securities in any state or jurisdiction in which may only be sold pursuant to an effective registration statement such offer, solicitation or sale would be unlawful prior to filed with the Securities and Exchange Commission (the “SEC”). registration or qualification under the securities laws of any such state or jurisdiction. The Company has filed with the SEC a registration statement (File No. 333-256572) including a preliminary prospectus for the Copies of the preliminary prospectus may be obtained for free offering to which this presentation relates, but such registration by visiting EDGAR on the SEC web site at www.sec.gov or by statement has not been declared effective. contacting ThinkEquity LLC, 17 State Street, 22nd Floor, New York, NY 10004, by telephone at (877) 436-3673 or by email at Before you invest, you should read the preliminary prospectus prospectus@think-equity.com. in that registration statement, including the “Risk Factors” set forth therein, and the documents filed as exhibits to the registration statement for more complete information about the Company and the offering. You may access these documents for free by visiting EDGAR on the SEC website at www.sec.gov. 3 Nasdaq: CNTXFree Writing Prospectus This Presentation is not an offer to sell, and is not seeking an This presentation shall not constitute an offer to sell or the offer to buy, any securities of Context Therapeutics Inc. (the solicitation of an offer to buy these securities, nor shall there be Company , or we, us, or our ). The Company's securities any sale of these securities in any state or jurisdiction in which may only be sold pursuant to an effective registration statement such offer, solicitation or sale would be unlawful prior to filed with the Securities and Exchange Commission (the “SEC”). registration or qualification under the securities laws of any such state or jurisdiction. The Company has filed with the SEC a registration statement (File No. 333-256572) including a preliminary prospectus for the Copies of the preliminary prospectus may be obtained for free offering to which this presentation relates, but such registration by visiting EDGAR on the SEC web site at www.sec.gov or by statement has not been declared effective. contacting ThinkEquity LLC, 17 State Street, 22nd Floor, New York, NY 10004, by telephone at (877) 436-3673 or by email at Before you invest, you should read the preliminary prospectus prospectus@think-equity.com. in that registration statement, including the “Risk Factors” set forth therein, and the documents filed as exhibits to the registration statement for more complete information about the Company and the offering. You may access these documents for free by visiting EDGAR on the SEC website at www.sec.gov. 3 Nasdaq: CNTX
Offering Summary Issuer Context Therapeutics Inc. Listing CNTX (NASDAQ Capital Markets) (1) Proposed Aggregate Offering $25,000,000 Price Range $5.00 per share Shares Offered 5,000,000 Pre-IPO Common Shares Outstanding 5,209,792 (2) as converted Advancing clinical development of ONA-XR, our lead PR antagonist for PR+ solid tumors, Use of Proceeds preclinical advancement of Claudin 6 bispecific, R&D working capital, general corporate Sole Book-Runner ThinkEquity (1) Anticipated gross proceeds are assuming a $5.00 initial public offering price and the sale of 5,000,000 shares of common stock (2) Common stock share total is as of September 1, 2021, after giving pro forma affect to the conversion of all outstanding shares of preferred stock and the conversion of certain warrants immediately prior to the completion of the initial public offering. 4 Nasdaq: CNTXOffering Summary Issuer Context Therapeutics Inc. Listing CNTX (NASDAQ Capital Markets) (1) Proposed Aggregate Offering $25,000,000 Price Range $5.00 per share Shares Offered 5,000,000 Pre-IPO Common Shares Outstanding 5,209,792 (2) as converted Advancing clinical development of ONA-XR, our lead PR antagonist for PR+ solid tumors, Use of Proceeds preclinical advancement of Claudin 6 bispecific, R&D working capital, general corporate Sole Book-Runner ThinkEquity (1) Anticipated gross proceeds are assuming a $5.00 initial public offering price and the sale of 5,000,000 shares of common stock (2) Common stock share total is as of September 1, 2021, after giving pro forma affect to the conversion of all outstanding shares of preferred stock and the conversion of certain warrants immediately prior to the completion of the initial public offering. 4 Nasdaq: CNTX
Executive Summary Executive Summary Our Focus → Women’s oncology → Onapristone extended release (ONA-XR) Lead Asset: → ONA-XR is a full progesterone receptor (PR) antagonist ONA-XR → PR oncogenic signaling associated with breast, ovarian, and endometrial cancer → ONA-XR in multiple clinical trials: • Three Phase 2 trials Focus on Execution • One Phase 1b/2 trial • Two Phase 0 biomarker studies → ONA-XR has been administered in over 128 subjects-to-date • Appears to be well tolerated, which supports continued development Path Forward • Designed to potentially enhance current therapeutics and reduce resistance to antiestrogen therapy • Straightforward clinical development plan 5 Nasdaq: CNTXExecutive Summary Executive Summary Our Focus → Women’s oncology → Onapristone extended release (ONA-XR) Lead Asset: → ONA-XR is a full progesterone receptor (PR) antagonist ONA-XR → PR oncogenic signaling associated with breast, ovarian, and endometrial cancer → ONA-XR in multiple clinical trials: • Three Phase 2 trials Focus on Execution • One Phase 1b/2 trial • Two Phase 0 biomarker studies → ONA-XR has been administered in over 128 subjects-to-date • Appears to be well tolerated, which supports continued development Path Forward • Designed to potentially enhance current therapeutics and reduce resistance to antiestrogen therapy • Straightforward clinical development plan 5 Nasdaq: CNTX
Executive Summary Progesterone Receptors Antagonism: Ready for Prime Time There is heightened interest in Development of PRAs ONA-XR is designed to PR antagonists (PRAs) for hindered by PK issues, address prior treating hormone-dependent poor selectivity, and mixed limitations of PRAs cancers due to new agonist/antagonist properties mechanistic understandings of PR oncogenic signaling ONA-XR is an opportunity to realize the potential of progesterone receptor antagonists in oncology 6 Nasdaq: CNTX
Executive Summary Market Opportunity for Lead Program (ONA-XR) • We target large, underserved markets • Within the G7 countries, over 355,000 patients are living with metastatic breast, ovarian, or endometrial cancer • Based upon published data, up to 70% of these patients are potentially eligible for ONA-XR treatment Prevalence of Metastatic Female Hormone-Driven Cancers in G7 Countries (EU5, Japan, US) 250,000 US EU5 JP2 35,000 200,000 150,000 104,000 100,000 12,000 11,000 50,000 89,000 30,000 28,000 28,000 25,000 - Breast Cancer Ovarian Cancer Endometrial Cancer *Source: secondary epidemiologic estimates, 2020 estimates 7 Nasdaq: CNTX PatientsExecutive Summary Market Opportunity for Lead Program (ONA-XR) • We target large, underserved markets • Within the G7 countries, over 355,000 patients are living with metastatic breast, ovarian, or endometrial cancer • Based upon published data, up to 70% of these patients are potentially eligible for ONA-XR treatment Prevalence of Metastatic Female Hormone-Driven Cancers in G7 Countries (EU5, Japan, US) 250,000 US EU5 JP2 35,000 200,000 150,000 104,000 100,000 12,000 11,000 50,000 89,000 30,000 28,000 28,000 25,000 - Breast Cancer Ovarian Cancer Endometrial Cancer *Source: secondary epidemiologic estimates, 2020 estimates 7 Nasdaq: CNTX Patients
Executive Summary Recent Drug Launches • Since 2012, there have been 5 major drug approvals, as shown below, for hormone-dependent breast cancer • We believe that ONA-XR will be additive or synergistic with these recently approved drugs, leading to a billion- dollar plus peak sales potential $14.4 Billion $1.4 Billion $0.8 Billion CDK4/6 Inhibitors PI3K Inhibitors mTOR Inhibitors Highest projected or historical annual peak sales for currently marketed products in breast cancer; includes 8 Nasdaq: CNTX historical years for drug classes with generic competition; based on data from EvaluatePharma as of July 2020Executive Summary Recent Drug Launches • Since 2012, there have been 5 major drug approvals, as shown below, for hormone-dependent breast cancer • We believe that ONA-XR will be additive or synergistic with these recently approved drugs, leading to a billion- dollar plus peak sales potential $14.4 Billion $1.4 Billion $0.8 Billion CDK4/6 Inhibitors PI3K Inhibitors mTOR Inhibitors Highest projected or historical annual peak sales for currently marketed products in breast cancer; includes 8 Nasdaq: CNTX historical years for drug classes with generic competition; based on data from EvaluatePharma as of July 2020
Executive Summary Focus on Execution Management • We believe that clinical development of ONA-XR is primarily a function of exacting clinical execution Evan Dick, PhD Martin Lehr Tarek Sahmoud, MD, PhD SVP R&D CEO and Director Chief Medical Officer • Context has an experienced • SVP, Aclaris Therapeutics • Independent Director, Praesidia Biologics • President, OncoStrategy LLC management team • SVP, Ralexar Therapeutics • Director, CureDuchenne Ventures • CMO, H3 Biomedicines • SVP, Ceptaris Therapeutics • Senior Associate, Osage University Partners • SVP, Celgene • SVP, Ception Therapeutics • SVP, Novartis Oncology • Our CMO led the clinical development of multiple blockbuster drugs for female cancers, including Kisqali, Arimidex, and Afinitor • Our management team is supported Eileen Kittrick, CPA Alex Levit, Esq Bill Rencher, PhD by a Board with strong public Controller Chief Legal Officer Head of CMC and Regulatory company operating and governance • Controller, Genova Group • Deputy GC, OptiNose • President, Drug Development Solutions LLC • Sr Dir, Siegfried Group • Associate GC, Teva experience • Senior Director, Fulcrum Pharma Dev • Auditor, Lindquist & Joyce • Associate, Reed Smith • Director, CONRAD Program • Assoc. Director, Schering Plough 9 Nasdaq: CNTXExecutive Summary Focus on Execution Management • We believe that clinical development of ONA-XR is primarily a function of exacting clinical execution Evan Dick, PhD Martin Lehr Tarek Sahmoud, MD, PhD SVP R&D CEO and Director Chief Medical Officer • Context has an experienced • SVP, Aclaris Therapeutics • Independent Director, Praesidia Biologics • President, OncoStrategy LLC management team • SVP, Ralexar Therapeutics • Director, CureDuchenne Ventures • CMO, H3 Biomedicines • SVP, Ceptaris Therapeutics • Senior Associate, Osage University Partners • SVP, Celgene • SVP, Ception Therapeutics • SVP, Novartis Oncology • Our CMO led the clinical development of multiple blockbuster drugs for female cancers, including Kisqali, Arimidex, and Afinitor • Our management team is supported Eileen Kittrick, CPA Alex Levit, Esq Bill Rencher, PhD by a Board with strong public Controller Chief Legal Officer Head of CMC and Regulatory company operating and governance • Controller, Genova Group • Deputy GC, OptiNose • President, Drug Development Solutions LLC • Sr Dir, Siegfried Group • Associate GC, Teva experience • Senior Director, Fulcrum Pharma Dev • Auditor, Lindquist & Joyce • Associate, Reed Smith • Director, CONRAD Program • Assoc. Director, Schering Plough 9 Nasdaq: CNTX
context t h e r a p e u t i c s ONA-XR Progesterone Receptor Antagonist 10 Nasdaq: CNTXcontext t h e r a p e u t i c s ONA-XR Progesterone Receptor Antagonist 10 Nasdaq: CNTX
ONA-XR ONA-XR is Being Developed to Enhance SOC Efficacy in Hormone-dependent Breast Cancer • The current standard of care (SOC) for primary, hormone-dependent breast cancer (ER+,PR+,HER2-) is antiestrogen therapy st 1 • The current 1 line SOC treatment for metastatic breast cancer is antiestrogen therapy plus a CDK4/6 inhibitor st 2 • Current therapeutic options are limited for patients whose disease continues to progress after 1 line therapy st nd • ONA-XR has the potential to enhance the efficacy of 1 line therapy, as well as that of 2 line and later line treatments Disease Progression * Enhance the Mitigate treatment We believe ONA-XR will enhance efficacy/duration of resistance in the response to first second and later efficacy of standard of care therapies line treatment line settings 1 * Adjuvant therapy is therapy that is given in addition to the primary or Rugo, JCO, 2016 11 Nasdaq: CNTX 2 initial therapy to maximize its effectiveness. Clarke, Mol and Cell Endo, 2015ONA-XR ONA-XR is Being Developed to Enhance SOC Efficacy in Hormone-dependent Breast Cancer • The current standard of care (SOC) for primary, hormone-dependent breast cancer (ER+,PR+,HER2-) is antiestrogen therapy st 1 • The current 1 line SOC treatment for metastatic breast cancer is antiestrogen therapy plus a CDK4/6 inhibitor st 2 • Current therapeutic options are limited for patients whose disease continues to progress after 1 line therapy st nd • ONA-XR has the potential to enhance the efficacy of 1 line therapy, as well as that of 2 line and later line treatments Disease Progression * Enhance the Mitigate treatment We believe ONA-XR will enhance efficacy/duration of resistance in the response to first second and later efficacy of standard of care therapies line treatment line settings 1 * Adjuvant therapy is therapy that is given in addition to the primary or Rugo, JCO, 2016 11 Nasdaq: CNTX 2 initial therapy to maximize its effectiveness. Clarke, Mol and Cell Endo, 2015
ONA-XR Progesterone Receptor (PR) Signaling is Oncogenic Hormone-Dependent Growth Factor-Mediated PR Signaling PR Signaling 1 • Cancer initiation Oncogenic 2 PR signaling • Metastatic spread Estrogen Progesterone Growth Factors (FGF, EGF) is associated • Resistance to current with: 2,3 therapies PI3K Ras ER PR A Mek Akt A • Wild-type or mutant Cyclin D1 Mek ESR1 PR estrogen receptor (ER) CDK4/6 B Oncogenic receptor activity Erk C PR signaling B • Progesterone-mediated can be driven signaling by: NUCLEUS C• Growth factor-mediated DNA signaling Oncogene transcription Onapristone blocks all forms of PR signaling 1 Knutson, J Hem Onc, 2017 2 Dwyer, Metastasis, 2021 12 Nasdaq: CNTX 3 Lopez-Knowles, BJC, 2018ONA-XR Progesterone Receptor (PR) Signaling is Oncogenic Hormone-Dependent Growth Factor-Mediated PR Signaling PR Signaling 1 • Cancer initiation Oncogenic 2 PR signaling • Metastatic spread Estrogen Progesterone Growth Factors (FGF, EGF) is associated • Resistance to current with: 2,3 therapies PI3K Ras ER PR A Mek Akt A • Wild-type or mutant Cyclin D1 Mek ESR1 PR estrogen receptor (ER) CDK4/6 B Oncogenic receptor activity Erk C PR signaling B • Progesterone-mediated can be driven signaling by: NUCLEUS C• Growth factor-mediated DNA signaling Oncogene transcription Onapristone blocks all forms of PR signaling 1 Knutson, J Hem Onc, 2017 2 Dwyer, Metastasis, 2021 12 Nasdaq: CNTX 3 Lopez-Knowles, BJC, 2018
ONA-XR Stereochemical Basis of Onapristone’s Full PR Antagonism → Onapristone is the only full PR antagonist (PRA) from among all clinically evaluated PRAs • Full PR antagonism means it exhibits no PR agonist activity → Onapristone’s full PRA activity is attributed, in part, to a unique spatial orientation or “stereochemistry” • The methyl group at the C-13 position is in a cis orientation for ONA compared to a trans orientation for all other drugs in its class cis trans orientation orientation at C-13 position at C-13 position 13 13 13 Onapristone Mifepristone ORIC-101 TM (Korlym ) (Oric Pharmaceuticals) Full PR antagonist Mixed PR agonist-antagonist 13 Nasdaq: CNTX
ONA-XR Patient-Derived Xenograft Data Addition of onapristone to standard of care drugs enhanced tumor regression PDX Xenograft PR+, PIK3CA mutant Placebo Ona Fulv Fulv Fulv Pal Ful Pal Ona Ona Pal Ona Triplet treatment: fulvestrant, onapristone, palbociclib → Onapristone, in triplet with standard of care drugs, produced a statistically significant enhancement of tumor regression compared to monotherapy and combination arms → Patient-derived xenograft (PDX) data supports the clinical evaluation of ONA-XR in combination with CDK4/6 inhibitors plus antiestrogen therapy Maragoni et al, Unpublished, 2021 Ona = onapristone; Fulv = fulvestrant; Pal = Palbociclib 14 Nasdaq: CNTX Relative tumor volume = 100( V - V )/V where V = initial tumor volume and V = final tumor volume f i i i f Relative Tumor Volume: (mean +/- SEM) Tumor Volume at Day 46 in individual xenografts: % volume change from baselineONA-XR Patient-Derived Xenograft Data Addition of onapristone to standard of care drugs enhanced tumor regression PDX Xenograft PR+, PIK3CA mutant Placebo Ona Fulv Fulv Fulv Pal Ful Pal Ona Ona Pal Ona Triplet treatment: fulvestrant, onapristone, palbociclib → Onapristone, in triplet with standard of care drugs, produced a statistically significant enhancement of tumor regression compared to monotherapy and combination arms → Patient-derived xenograft (PDX) data supports the clinical evaluation of ONA-XR in combination with CDK4/6 inhibitors plus antiestrogen therapy Maragoni et al, Unpublished, 2021 Ona = onapristone; Fulv = fulvestrant; Pal = Palbociclib 14 Nasdaq: CNTX Relative tumor volume = 100( V - V )/V where V = initial tumor volume and V = final tumor volume f i i i f Relative Tumor Volume: (mean +/- SEM) Tumor Volume at Day 46 in individual xenografts: % volume change from baseline
ONA-XR Promising Evidence of Clinical Efficacy as a First-Line Rx in Breast Cancer Onapristone Immediate Release (ONA-IR) as First Line Therapy → Onapristone in an immediate release formulation 68% (ONA-IR) had a meaningful impact on treatment of 66% 66% hormone-dependent breast cancer 64% → In 1999, Robertson et al reported that ONA-IR 62% 60% showed promising efficacy as a first line therapy 58% for localized or metastatic breast cancer, but with 1 55% 56% “…transient liver function test abnormalities” 54% 52% → ONA-XR was designed to minimize liver function 50% test abnormalities and enable onapristone to be 48% evaluated again, for efficacy/safety in hormone- ORR (%) CBR (%) dependent cancers overall response rate (ORR) and clinical benefit rate (CBR) 1 in locally advanced or metastatic breast cancer 1 Robertson, Eur J Cancer, 1999 15 Nasdaq: CNTX ORR = overall response rate; CBR = clinical benefit rateONA-XR Promising Evidence of Clinical Efficacy as a First-Line Rx in Breast Cancer Onapristone Immediate Release (ONA-IR) as First Line Therapy → Onapristone in an immediate release formulation 68% (ONA-IR) had a meaningful impact on treatment of 66% 66% hormone-dependent breast cancer 64% → In 1999, Robertson et al reported that ONA-IR 62% 60% showed promising efficacy as a first line therapy 58% for localized or metastatic breast cancer, but with 1 55% 56% “…transient liver function test abnormalities” 54% 52% → ONA-XR was designed to minimize liver function 50% test abnormalities and enable onapristone to be 48% evaluated again, for efficacy/safety in hormone- ORR (%) CBR (%) dependent cancers overall response rate (ORR) and clinical benefit rate (CBR) 1 in locally advanced or metastatic breast cancer 1 Robertson, Eur J Cancer, 1999 15 Nasdaq: CNTX ORR = overall response rate; CBR = clinical benefit rate
ONA-XR ONA-XR Was Designed to Improve Therapeutic Window of ONA-IR ONA-XR versus ONA-IR: plasma onapristone 1 concentrations at Day 1 and at steady-state → PK dataset enabled a direct comparison between C and steady-state trough concentrations (C ) max min-ss ONA-IR 100 mg QD, Day 1 ONA-IR 100mg QD and ONA-XR 50mg BID ONA-XR 50 mg BID, Day 1 ONA-IR 100 mg QD, steady state → Dosing with ONA-XR resulted in a steady-state ONA-XR 50 mg BID, steady state C almost 3X lower than for ONA-IR max ONA-IR 100 mg QD mean Cmin (steady-state → Steady-state C was similar for both onapristone min formulations Compared to ONA-IR, ONA-XR has: • Lower peak drug concentration (C ) to improve max tolerability • Similar trough drug concentration (C ) to maintain min target coverage and efficacy 1 Lewis, Drug Safety, July 2020 16 Nasdaq: CNTXONA-XR ONA-XR Was Designed to Improve Therapeutic Window of ONA-IR ONA-XR versus ONA-IR: plasma onapristone 1 concentrations at Day 1 and at steady-state → PK dataset enabled a direct comparison between C and steady-state trough concentrations (C ) max min-ss ONA-IR 100 mg QD, Day 1 ONA-IR 100mg QD and ONA-XR 50mg BID ONA-XR 50 mg BID, Day 1 ONA-IR 100 mg QD, steady state → Dosing with ONA-XR resulted in a steady-state ONA-XR 50 mg BID, steady state C almost 3X lower than for ONA-IR max ONA-IR 100 mg QD mean Cmin (steady-state → Steady-state C was similar for both onapristone min formulations Compared to ONA-IR, ONA-XR has: • Lower peak drug concentration (C ) to improve max tolerability • Similar trough drug concentration (C ) to maintain min target coverage and efficacy 1 Lewis, Drug Safety, July 2020 16 Nasdaq: CNTX
ONA-XR ONA-XR Evaluation in Breast Cancer Trials Treatment Estimated Standard of Care Line Context Trial Trial Status Patients (US)* (SOC) Medical Need Enrollment Adjuvant Completed; Window of Enhance antiestrogen potency; (after primary >>250,000 Antiestrogen 1 Opportunity decrease progression to TNBC disease Presentation treatment) Q4 2021 1L Identify and treat 20% of First-Line ER+,PR+,HER2- Enrolling Patients 75,000 Antiestrogen + CDK4/6i patients who are at high risk of Metastatic high 2 (ctDNA ) early relapse Second / 2L/3L Fulvestrant or Weak tumor response ER+,PR+,HER2- Enrolling Patients 35,000 Third Line Fulvestrant + PI3Ka to current SOC 3 (post-CDK4/6i) Metastatic Our breast cancer trials build upon positive Phase 1-2 data from ONA-IR trials (1) NCT04142892; (2) NCT04872608; (3) NCT04738292 17 Nasdaq: CNTX *Source: secondary epidemiologic estimates, 2020 estimatesONA-XR ONA-XR Evaluation in Breast Cancer Trials Treatment Estimated Standard of Care Line Context Trial Trial Status Patients (US)* (SOC) Medical Need Enrollment Adjuvant Completed; Window of Enhance antiestrogen potency; (after primary >>250,000 Antiestrogen 1 Opportunity decrease progression to TNBC disease Presentation treatment) Q4 2021 1L Identify and treat 20% of First-Line ER+,PR+,HER2- Enrolling Patients 75,000 Antiestrogen + CDK4/6i patients who are at high risk of Metastatic high 2 (ctDNA ) early relapse Second / 2L/3L Fulvestrant or Weak tumor response ER+,PR+,HER2- Enrolling Patients 35,000 Third Line Fulvestrant + PI3Ka to current SOC 3 (post-CDK4/6i) Metastatic Our breast cancer trials build upon positive Phase 1-2 data from ONA-IR trials (1) NCT04142892; (2) NCT04872608; (3) NCT04738292 17 Nasdaq: CNTX *Source: secondary epidemiologic estimates, 2020 estimates
ONA-XR ONA-XR Evaluation in Gynecologic Trials Estimated Standard of Care Cancer Context Trial Trial Status Patients (US)* (SOC) Medical Need Combination with Limited treatment Recurrent Anastrozole in PR+ Enrolling Patients 25,000 Lenvima + Keytruda options after Endometrial 1 patients recurrence Monotherapy Phase Recurrent Combination with No FDA approved Complete; Granulosa Cell Anastrozole in PR+ 5,000 Physician’s Choice products in recurrent 2 Combination Study Tumor of Ovary patients setting Enrolling Patients Focused on gynecologic malignancies where PR is a known driver (1) NCT04719273; (2) NCT03909152 18 Nasdaq: CNTX *Source: secondary epidemiologic estimates, 2020 estimates
Granulosa Cell Tumor of Ovary Granulosa Cell Tumor (GCT) of Ovary: A White Space Opportunity • GCT of Ovary are Rare Tumors 3 – Estimated 5,000 patients with recurrent disease in US 1,2 – Almost 100% are progesterone receptor (PR) positive • Current Treatment Options are Limited 3 – Primary treatment is cytoreductive surgery and platinum-based chemotherapy 3 – No FDA approved treatments for recurrent GCT 4 – Antiestrogen use is common, but rarely results in tumor shrinkage • Program Status and Next Steps – Completed enrollment of late line patients with ONA-XR monotherapy (n = 14 patients) – Ongoing treatment of early line patients with ONA-XR plus antiestrogen therapy (n = 25 patients) Context has the only open clinical trial in the United States 1 3 Puechl, Gynecol. Oncol.,2019 Farinola, Int. J. Gynecol. Pathol.,2007 19 Nasdaq: CNTX 2 4 Schumer, Gynecol. Oncol.,2003 Banerjee, JCO, 2018Granulosa Cell Tumor of Ovary Granulosa Cell Tumor (GCT) of Ovary: A White Space Opportunity • GCT of Ovary are Rare Tumors 3 – Estimated 5,000 patients with recurrent disease in US 1,2 – Almost 100% are progesterone receptor (PR) positive • Current Treatment Options are Limited 3 – Primary treatment is cytoreductive surgery and platinum-based chemotherapy 3 – No FDA approved treatments for recurrent GCT 4 – Antiestrogen use is common, but rarely results in tumor shrinkage • Program Status and Next Steps – Completed enrollment of late line patients with ONA-XR monotherapy (n = 14 patients) – Ongoing treatment of early line patients with ONA-XR plus antiestrogen therapy (n = 25 patients) Context has the only open clinical trial in the United States 1 3 Puechl, Gynecol. Oncol.,2019 Farinola, Int. J. Gynecol. Pathol.,2007 19 Nasdaq: CNTX 2 4 Schumer, Gynecol. Oncol.,2003 Banerjee, JCO, 2018
Granulosa Cell Tumor of Ovary ONA-XR in Late Line Granulosa Cell Tumors of the Ovary Durability of Prior Therapies %, Median prior therapy (Range) 15 Overall 4 (1-17) Durability of Prior Therapy 14 Letrozole + ketoconazole (5 mos) Chemotherapy 1.5 (1-8) 13 Lupron + Cyclophosphamide (2 mos) Antiestrogen 2.5 (0-11) 12 Anastrozole (7 mos) 12 11 Letrozole (7 mos) Prior Response % (n) 11 Letrozole (3 mos) 10 Treatment Free Interval 10 < 6 months 93% (13) 9 Carboplatin + Gemcitibine (4 mos) 6-12months 0%(0) 9 Anastrozole (100 mos) 8 > 12 months 7%(1) 8 7 Lupron (23 mos) 7 6 Tamoxifen + Megace (7 mos) Response % (n) 6 5 Letrozole (6 mos) Stable Disease 64%(9) ProgressiveDisease 29%(4) 5 4 Doxil (2 mos) Not Assessed 7% (1) 3 4 Bevacizumab (7 mos) 2 3 Carboplatin + Taxol (5 mos) Overall Durability % (n) 1 2 Duration of Treatment (Weeks) Etopside (2 mos) * Pts on study ≥ 16weeks 42%(6) 0 1 Pts on study ≥ 24weeks 29%(4) 0 12 24 36 48 60 72 84 → Two patients remain on therapy with stable disease Late line data supports evaluating → 64% of patients had stable disease ONA-XR earlier in patient treatment → Excellent safety and tolerability * Progression due to disease-relatedAE 20 Nasdaq: CNTX Data Cutoff August 2, 2021 ≥ 3 lines ≤ 6 mos prior Rx Chemotherapy AntihormonalGranulosa Cell Tumor of Ovary ONA-XR in Late Line Granulosa Cell Tumors of the Ovary Durability of Prior Therapies %, Median prior therapy (Range) 15 Overall 4 (1-17) Durability of Prior Therapy 14 Letrozole + ketoconazole (5 mos) Chemotherapy 1.5 (1-8) 13 Lupron + Cyclophosphamide (2 mos) Antiestrogen 2.5 (0-11) 12 Anastrozole (7 mos) 12 11 Letrozole (7 mos) Prior Response % (n) 11 Letrozole (3 mos) 10 Treatment Free Interval 10 < 6 months 93% (13) 9 Carboplatin + Gemcitibine (4 mos) 6-12months 0%(0) 9 Anastrozole (100 mos) 8 > 12 months 7%(1) 8 7 Lupron (23 mos) 7 6 Tamoxifen + Megace (7 mos) Response % (n) 6 5 Letrozole (6 mos) Stable Disease 64%(9) ProgressiveDisease 29%(4) 5 4 Doxil (2 mos) Not Assessed 7% (1) 3 4 Bevacizumab (7 mos) 2 3 Carboplatin + Taxol (5 mos) Overall Durability % (n) 1 2 Duration of Treatment (Weeks) Etopside (2 mos) * Pts on study ≥ 16weeks 42%(6) 0 1 Pts on study ≥ 24weeks 29%(4) 0 12 24 36 48 60 72 84 → Two patients remain on therapy with stable disease Late line data supports evaluating → 64% of patients had stable disease ONA-XR earlier in patient treatment → Excellent safety and tolerability * Progression due to disease-relatedAE 20 Nasdaq: CNTX Data Cutoff August 2, 2021 ≥ 3 lines ≤ 6 mos prior Rx Chemotherapy Antihormonal
ONA-XR Summary ONA-XR • ONA-XR is the only full progesterone receptor (PR) antagonist in clinical development • Clinical activity established with ONA-IR, new data emerging with ONA-XR • ONA-XR has superior safety profile to ONA-IR • IP protection through at least 2034 Market • Hormone-dependent cancer (breast, ovarian, endometrial) are large and growing markets Opportunity • Progesterone receptor antagonism (PRA) represents a new approach • PRA may be used alone or in combination to enhance the efficacy/durability of therapeutics used as the standard of care Value • Three Phase 2 trials Creation • One Phase 1b/2 trial • Two Phase 0 biomarker trials • Incorporation of ctDNA for an early read on clinical response to ONA-XR 21 Nasdaq: CNTXONA-XR Summary ONA-XR • ONA-XR is the only full progesterone receptor (PR) antagonist in clinical development • Clinical activity established with ONA-IR, new data emerging with ONA-XR • ONA-XR has superior safety profile to ONA-IR • IP protection through at least 2034 Market • Hormone-dependent cancer (breast, ovarian, endometrial) are large and growing markets Opportunity • Progesterone receptor antagonism (PRA) represents a new approach • PRA may be used alone or in combination to enhance the efficacy/durability of therapeutics used as the standard of care Value • Three Phase 2 trials Creation • One Phase 1b/2 trial • Two Phase 0 biomarker trials • Incorporation of ctDNA for an early read on clinical response to ONA-XR 21 Nasdaq: CNTX
context t h e r a p e u t i c s Claudin 6 Program 22 Nasdaq: CNTXcontext t h e r a p e u t i c s Claudin 6 Program 22 Nasdaq: CNTX
Claudin 6 CLDN6 x CD3 Bispecific Antibody The bispecific antibody simultaneously binds to a CLDN6- • A “pure” cancer target expressing tumor cell and a cytotoxic T-cell. This brings the ̶ Claudin-6 (CLDN6) is an oncofetal protein expressed in several tumor types, T-cell into close proximity to the tumor cell, triggering tumor cell but NOT in normal adult tissues apoptosis via the release of cytotoxic elements. • Claudin-6 is expressed in ovarian, endometrial, lung, and gastric Tumor cell T cell cancers Lysis • Target selectivity is a challenge – and a differentiator in the field ̶ CLDN6 is structurally similar to CLDN9, differing by only 3 amino acids in the CLDN6 CD3 extracellular domain Cytotoxic cytokines ̶ Target selectivity is paramount, because CLDN9 is required for normal hearing 1,2 and maintenance of the gut • Precedent for targeting a claudin-family oncofetal protein ̶ CLDN18.2 is, like CLDN6, a oncofetal protein. In adults, CLDN18.2 is expressed in gastric and pancreatic adenocarcinomas, but otherwise limited to the epithelium of the stomach ̶ Strong results treating gastric cancers with naked anti-CLDN18.2, as well as CLDN6 x CD3 CLDN18.2-based bispecific antibodies has led to an expansion to 24 clinical trials bispecific antibody ̶ The technical principles for targeting CLDN6 are very similar to those for targeting CLDN18.2 1 Sineni, Hum Genet, 2019 23 Nasdaq: CNTX 2 Vecchio, PNAS, 2019Claudin 6 CLDN6 x CD3 Bispecific Antibody The bispecific antibody simultaneously binds to a CLDN6- • A “pure” cancer target expressing tumor cell and a cytotoxic T-cell. This brings the ̶ Claudin-6 (CLDN6) is an oncofetal protein expressed in several tumor types, T-cell into close proximity to the tumor cell, triggering tumor cell but NOT in normal adult tissues apoptosis via the release of cytotoxic elements. • Claudin-6 is expressed in ovarian, endometrial, lung, and gastric Tumor cell T cell cancers Lysis • Target selectivity is a challenge – and a differentiator in the field ̶ CLDN6 is structurally similar to CLDN9, differing by only 3 amino acids in the CLDN6 CD3 extracellular domain Cytotoxic cytokines ̶ Target selectivity is paramount, because CLDN9 is required for normal hearing 1,2 and maintenance of the gut • Precedent for targeting a claudin-family oncofetal protein ̶ CLDN18.2 is, like CLDN6, a oncofetal protein. In adults, CLDN18.2 is expressed in gastric and pancreatic adenocarcinomas, but otherwise limited to the epithelium of the stomach ̶ Strong results treating gastric cancers with naked anti-CLDN18.2, as well as CLDN6 x CD3 CLDN18.2-based bispecific antibodies has led to an expansion to 24 clinical trials bispecific antibody ̶ The technical principles for targeting CLDN6 are very similar to those for targeting CLDN18.2 1 Sineni, Hum Genet, 2019 23 Nasdaq: CNTX 2 Vecchio, PNAS, 2019
Claudin 6 CLDN6 x CD3 Bispecific Retains Selectivity of Parental mAb CLDN6 Binding CLDN9 Binding 4 5 3×10 3×10 IM-271-1HHP Antibody (IgG) Clinical Benchmark (IgG) Context Antibody (IgG) BioNTech Antibody (IgG) IM-271-1HHP (IgG) IMC-20-4 (bispecific) Context (bispecific) Context Antibody (IgG) IMC-20-4 (bispecific) Context (bispecific) 5 4 Equivalent BioNTech 2×10 2×10 Affinity 5 4 Context 1×10 1×10 0 0 -12 -11 -10 -9 -8 -7 -6 -12 -11 -10 -9 -8 -7 -6 Log [antibody] (M) Log10 [Ab] (M) Anti-CLDN6 mAb versus CLDN6xCD3 bispecific antibody: Anti-CLDN6 mAbs versus CLDN6xCD3 bispecific antibody: binding to CLDN6-expressing cells binding to CLDN9-expressing cells → CLDN9 binding of Context bispecific is not significantly different from that of its parent anti-CLDN6 mAb → CLDN6 binding affinity of bispecific is not significantly different from its parental anti-CLDN6 mAb → BioNTech mAb shows higher CLDN9 binding than either the parent Context mAb or the Context bispecific antibody 24 Nasdaq: CNTX CLDN6 Cell Binding (mean channel fluorescence) CLDN9 Cell Binding (mean channel fluorescence)
Claudin 6 Context Bispecifics Activate T Cells Against CLDN6+ Cells T Cell Activation T Cell Dependent Cytotoxicity • Context bispecifics activate T-cells as determined by T-cell expression of CD25 • Context bispecifics drive T-cell dependent cytotoxicity • Background activation (PBMCs alone) is not significantly different from • Background cytotoxicity (PBMCs alone) is not significantly different from the PBMCs plus a control bispecific several controls • Significant activation is seen in the presence of PBMCs plus either Context • Significant cytotoxicity is seen in the presence of PBMCs plus either Context CLDN6xCD3 bispecifics or the BioNTech bispecific (red bars) CLDN6xCD3 bispecifics or the BioNTech bispecific (red bars) Context CLDN6-selective bispecifics induce T-cell activation and T-cell mediated cytotoxicity against CLDN6-expressing cells Study Design: formats all contain same CD3 arms; activity measured after 72 hours 25 Nasdaq: CNTXClaudin 6 Context Bispecifics Activate T Cells Against CLDN6+ Cells T Cell Activation T Cell Dependent Cytotoxicity • Context bispecifics activate T-cells as determined by T-cell expression of CD25 • Context bispecifics drive T-cell dependent cytotoxicity • Background activation (PBMCs alone) is not significantly different from • Background cytotoxicity (PBMCs alone) is not significantly different from the PBMCs plus a control bispecific several controls • Significant activation is seen in the presence of PBMCs plus either Context • Significant cytotoxicity is seen in the presence of PBMCs plus either Context CLDN6xCD3 bispecifics or the BioNTech bispecific (red bars) CLDN6xCD3 bispecifics or the BioNTech bispecific (red bars) Context CLDN6-selective bispecifics induce T-cell activation and T-cell mediated cytotoxicity against CLDN6-expressing cells Study Design: formats all contain same CD3 arms; activity measured after 72 hours 25 Nasdaq: CNTX
Claudin 6 Competitive Landscape/Advantage • Context anti-CLDN6 binding is at least 10x more selective vs. CLDN9 than competitive anti-CLDN6 mAbs and bispecifics • CLDN6:CLDN9 binding selectivity is a critical safety factor for CLDN6-targeted bispecific antibodies Context Xencor BioNTech BNT211 Program Confidential Confidential BNT142 CLDN6xCD3 CLDN6xCD3 CLDN6 CAR-T, Antibody Format Bispecific Bispecific CLDN6xCD3 (bi(sFc)) Phase 1, Stage Preclinical Preclinical Phase 1 2 Status Active Active Active Selectivity 1 >100x 10x 7x CLDN6:9 The Company has performed head-to-head in vitro studies comparing BioNTech CLDN6 monoclonal antibodies. These antibodies were derived from publicly available reports published independent of the Company and may differ in material ways from the actual antibody that is in development. (1) Faber et al., Proceedings: AACR Annual Meeting 2021; April 9-14, 2021 26 Nasdaq: CNTX (2) BNT211: NCT04503278; BNT142 Ph 1 initiation 2H 2021 (ref: BioNTech Corp Presentation June 1, 2021) Claudin 6 Competitive Landscape/Advantage • Context anti-CLDN6 binding is at least 10x more selective vs. CLDN9 than competitive anti-CLDN6 mAbs and bispecifics • CLDN6:CLDN9 binding selectivity is a critical safety factor for CLDN6-targeted bispecific antibodies Context Xencor BioNTech BNT211 Program Confidential Confidential BNT142 CLDN6xCD3 CLDN6xCD3 CLDN6 CAR-T, Antibody Format Bispecific Bispecific CLDN6xCD3 (bi(sFc)) Phase 1, Stage Preclinical Preclinical Phase 1 2 Status Active Active Active Selectivity 1 >100x 10x 7x CLDN6:9 The Company has performed head-to-head in vitro studies comparing BioNTech CLDN6 monoclonal antibodies. These antibodies were derived from publicly available reports published independent of the Company and may differ in material ways from the actual antibody that is in development. (1) Faber et al., Proceedings: AACR Annual Meeting 2021; April 9-14, 2021 26 Nasdaq: CNTX (2) BNT211: NCT04503278; BNT142 Ph 1 initiation 2H 2021 (ref: BioNTech Corp Presentation June 1, 2021)
Claudin 6 Summary Claudin-6 is a tumor-specific protein in adults Integrating Claudin-6 binding with the CD3 T-cell engager couples immunotherapy to tumor specific targeting st nd Opportunity to be 1 /2 in market based on current competition Entering IND-enabling studies in 2022 27 Nasdaq: CNTXClaudin 6 Summary Claudin-6 is a tumor-specific protein in adults Integrating Claudin-6 binding with the CD3 T-cell engager couples immunotherapy to tumor specific targeting st nd Opportunity to be 1 /2 in market based on current competition Entering IND-enabling studies in 2022 27 Nasdaq: CNTX
context t h e r a p e u t i c s Corporate 28 Nasdaq: CNTXcontext t h e r a p e u t i c s Corporate 28 Nasdaq: CNTX
Executive Summary Pipeline FDA Cancer Clinical Indication Research Phase 1 Phase 2 Phase 3 Upcoming Milestones Fast Track 1 ONA-XR (PR antagonist) 1L ER+,PR+,HER2- • First patient Q3 2021 Phase 1b/2 Trial high ctDNA • Phase 1b data 1H 2022 Breast Cancer • First patient Q3 2021 2L/3L ER+,PR+,HER2- Phase 2 Trial Post-CDK4/6 inhibitor • Preliminary data 2H 2022 Ovarian Phase 2 Trial Recurrent PR+ Granulosa Cell • Preliminary data Mid 2022 Cancer Endometrial Phase 2 Trial Recurrent PR+ Endometrioid • Preliminary data 2H 2022 Cancer CLDN6xCD3 bispecific antibody Ovarian & Endometrial Cancer • IND enabling studies 2022 (1) Tyligand Biosciences Ltd licensed rights to ONA-XR in China, HK, Macau 29 Nasdaq: CNTXExecutive Summary Pipeline FDA Cancer Clinical Indication Research Phase 1 Phase 2 Phase 3 Upcoming Milestones Fast Track 1 ONA-XR (PR antagonist) 1L ER+,PR+,HER2- • First patient Q3 2021 Phase 1b/2 Trial high ctDNA • Phase 1b data 1H 2022 Breast Cancer • First patient Q3 2021 2L/3L ER+,PR+,HER2- Phase 2 Trial Post-CDK4/6 inhibitor • Preliminary data 2H 2022 Ovarian Phase 2 Trial Recurrent PR+ Granulosa Cell • Preliminary data Mid 2022 Cancer Endometrial Phase 2 Trial Recurrent PR+ Endometrioid • Preliminary data 2H 2022 Cancer CLDN6xCD3 bispecific antibody Ovarian & Endometrial Cancer • IND enabling studies 2022 (1) Tyligand Biosciences Ltd licensed rights to ONA-XR in China, HK, Macau 29 Nasdaq: CNTX
Corporate (1) Anticipated Use of Proceeds: $21.0 million Capital Activity Description (2) Allocation ONA-XR development, including our three ongoing Clinical Development ~$9.5 million Phase 2 trials and our ongoing Phase 1b/2 trial Preclinical Development CLDN6xCD3 bsAb development ~5.5 million General Corporate and Corporate expenses ~$6.0 million Working Capital (1) Anticipated net proceeds are assuming a $5.00 initial public offering price and the sale of 5,000,00 shares of common stock, after deducting underwriting discounts and commissions and estimated offering expenses payable by us. (2) Our expected use of gross proceeds represents our intentions based upon our current plans and business conditions. However, we cannot predict with certainty all of the particular uses for the net proceeds or the amounts that we will actually spend on the uses set forth above. 30 Nasdaq: CNTXCorporate (1) Anticipated Use of Proceeds: $21.0 million Capital Activity Description (2) Allocation ONA-XR development, including our three ongoing Clinical Development ~$9.5 million Phase 2 trials and our ongoing Phase 1b/2 trial Preclinical Development CLDN6xCD3 bsAb development ~5.5 million General Corporate and Corporate expenses ~$6.0 million Working Capital (1) Anticipated net proceeds are assuming a $5.00 initial public offering price and the sale of 5,000,00 shares of common stock, after deducting underwriting discounts and commissions and estimated offering expenses payable by us. (2) Our expected use of gross proceeds represents our intentions based upon our current plans and business conditions. However, we cannot predict with certainty all of the particular uses for the net proceeds or the amounts that we will actually spend on the uses set forth above. 30 Nasdaq: CNTX
Upcoming Milestones Q3 2021 Q4 2021 1H 2022 2H 2022 ONA-XR Breast – 1L (ctDNA enriched) Phase 1b trial update Breast – 2L/3L (post-CDK4/6) Phase 2 trial update Breast – Window of Opportunity data presentation Breast – PDX mechanism of action data Granulosa Cell – monotherapy Phase 2 trial update Granulosa Cell – combination Phase 2 trial update Endometrial – Phase 2 trial update Q3 2021 Q4 2021 1H 2022 2H 2022 Claudin 6 Nominate clinical development candidate 31 Nasdaq: CNTXUpcoming Milestones Q3 2021 Q4 2021 1H 2022 2H 2022 ONA-XR Breast – 1L (ctDNA enriched) Phase 1b trial update Breast – 2L/3L (post-CDK4/6) Phase 2 trial update Breast – Window of Opportunity data presentation Breast – PDX mechanism of action data Granulosa Cell – monotherapy Phase 2 trial update Granulosa Cell – combination Phase 2 trial update Endometrial – Phase 2 trial update Q3 2021 Q4 2021 1H 2022 2H 2022 Claudin 6 Nominate clinical development candidate 31 Nasdaq: CNTX
Corporate Cap Table Valuation Valuation drivers are: Capitalization 5,209,792 (1) Common Stock ONA-XR Multiple Phase 2 trial readouts (2) Options 436,437 Claudin 6 Precision medicine meets immunotherapy Fully Diluted Common 5,646,229 Business Development Opportunistic pipeline expansion Experienced Team Multiple FDA approvals in female cancers (1) Common stock share total is as of September 1, 2021, after giving pro forma effect to the conversion of all outstanding shares of preferred stock and the conversion of certain warrants immediately prior to the completion of the initial public offering. (2) Shares of common stock subject to options is as of September 1, 2021. The weighted average exercise of such option is $5.69 per share. 32 Nasdaq: CNTXCorporate Cap Table Valuation Valuation drivers are: Capitalization 5,209,792 (1) Common Stock ONA-XR Multiple Phase 2 trial readouts (2) Options 436,437 Claudin 6 Precision medicine meets immunotherapy Fully Diluted Common 5,646,229 Business Development Opportunistic pipeline expansion Experienced Team Multiple FDA approvals in female cancers (1) Common stock share total is as of September 1, 2021, after giving pro forma effect to the conversion of all outstanding shares of preferred stock and the conversion of certain warrants immediately prior to the completion of the initial public offering. (2) Shares of common stock subject to options is as of September 1, 2021. The weighted average exercise of such option is $5.69 per share. 32 Nasdaq: CNTX
Corporate Investment Highlights Large Unmet Need Female Cancers High Value Targets Progesterone Receptor and Claudin 6 Lead Product Candidate ONA-XR Being Evaluated in Multiple Phase 2 Trials Strong Team Deep Domain Experience, Track Record of Success Near-Term Milestones Multiple Data Readouts in 2022 33 Nasdaq: CNTX
Advancing Medicines context for Female Cancers th er ap eu tic s context 34 © CONTEXT THERAPEUTICS 2021 Nasdaq: CNTXAdvancing Medicines context for Female Cancers th er ap eu tic s context 34 © CONTEXT THERAPEUTICS 2021 Nasdaq: CNTX
context t h e r a p e u t i c s Appendix 35 Nasdaq: CNTXcontext t h e r a p e u t i c s Appendix 35 Nasdaq: CNTX
Appendix Abbreviations AR Androgen Receptor ctDNA Circulating tumor DNA ER Estrogen receptor ESR1 Estrogen receptor 1 gene Ful Fulvestrant GR Glucocorticoid Receptor MAPK Mitogen activated protein kinase mBCa Metastatic breast cancer ONA-IR Onapristone immediate release ONA-XR Onapristone extended release ORR Overall response rate PFS Progression free survival PR Progesterone receptor PR+ Progesterone receptor positive SERD Selective estrogen receptor degrader SoC Standard of Care WT Wild type 36 Nasdaq: CNTXAppendix Abbreviations AR Androgen Receptor ctDNA Circulating tumor DNA ER Estrogen receptor ESR1 Estrogen receptor 1 gene Ful Fulvestrant GR Glucocorticoid Receptor MAPK Mitogen activated protein kinase mBCa Metastatic breast cancer ONA-IR Onapristone immediate release ONA-XR Onapristone extended release ORR Overall response rate PFS Progression free survival PR Progesterone receptor PR+ Progesterone receptor positive SERD Selective estrogen receptor degrader SoC Standard of Care WT Wild type 36 Nasdaq: CNTX
Role of Progesterone in Cancer Epidemiologic Evidence: Progesterone Increases Breast Cancer Risk Progesterone promotes oncogenic progression and maintenance of stem cells, creating a reservoir of pre-malignant cells to seed metastasis. Initial evidence for this tumorigenic role is derived from longitudinal studies of the use of hormone replacement therapy in menopausal women. These studies determined that estrogen was correlated with a 23% decrease in cancer risk, whereas progesterone was correlated with a 25% increase in cancer risk (Horwitz 2008, Anderson 2012). The conclusion of this finding is that blocking progesterone function via anti-progestin therapy may be beneficial in cancer patients. 37 Nasdaq: CNTXRole of Progesterone in Cancer Epidemiologic Evidence: Progesterone Increases Breast Cancer Risk Progesterone promotes oncogenic progression and maintenance of stem cells, creating a reservoir of pre-malignant cells to seed metastasis. Initial evidence for this tumorigenic role is derived from longitudinal studies of the use of hormone replacement therapy in menopausal women. These studies determined that estrogen was correlated with a 23% decrease in cancer risk, whereas progesterone was correlated with a 25% increase in cancer risk (Horwitz 2008, Anderson 2012). The conclusion of this finding is that blocking progesterone function via anti-progestin therapy may be beneficial in cancer patients. 37 Nasdaq: CNTX
Role of Progesterone in Cancer Target Validation: In Vivo Models 80% 450 14 75% 400 12 350 10 MPA 300 8 Control 250 6 200 4 150 100 2 50 0 Number of Mice With Tumors Proliferative Index of Tumors 0 (n=20 per arm) (Mean BrdU as %) 0 10 20 30 Days WT PR KO Progesterone Receptor Knockout (PR KO) Inhibits Tumors Progesterone Stimulates Tumors Carcinogen treated, 7,12 dimethylbenz(a)anthracene (DMBA), pituitary- Progestin-induced mammary carcinomas were subcutaneously transplanted into isografted mice, there was a marked reduction in mammary tumor incidence the flank of female BALB/c mice treated or non-treated with synthetic at week 44 in PRKO mice as compared with isogenic wild types (WT). progesterone - medroxyprogesterone acetate (MPA). (Adapted from Lydon) (Adapted from Lanari) Progesterone Receptor Regulates Tumor Growth : Lydon, Cancer Research, 1999 38 Nasdaq: CNTX Lanari, Endocrine-Related Cancer, 2009 Tumor Volume (mm3)Role of Progesterone in Cancer Target Validation: In Vivo Models 80% 450 14 75% 400 12 350 10 MPA 300 8 Control 250 6 200 4 150 100 2 50 0 Number of Mice With Tumors Proliferative Index of Tumors 0 (n=20 per arm) (Mean BrdU as %) 0 10 20 30 Days WT PR KO Progesterone Receptor Knockout (PR KO) Inhibits Tumors Progesterone Stimulates Tumors Carcinogen treated, 7,12 dimethylbenz(a)anthracene (DMBA), pituitary- Progestin-induced mammary carcinomas were subcutaneously transplanted into isografted mice, there was a marked reduction in mammary tumor incidence the flank of female BALB/c mice treated or non-treated with synthetic at week 44 in PRKO mice as compared with isogenic wild types (WT). progesterone - medroxyprogesterone acetate (MPA). (Adapted from Lydon) (Adapted from Lanari) Progesterone Receptor Regulates Tumor Growth : Lydon, Cancer Research, 1999 38 Nasdaq: CNTX Lanari, Endocrine-Related Cancer, 2009 Tumor Volume (mm3)
Rationale for ONA-XR ONA-XR Active in Hard-to-Treat ESR1 Mutations 1,2 • 20-35% of ER+,PR+,HER2- metastatic breast tumors are ESR1 mutated (hyperactive estrogen receptor) 1,2 • Estrogen receptor mutations are associated with resistance to anti-estrogen + CDK4/6i therapy 3 • ESR1 mutations stimulate PR expression and induce PR activity ESR1 Mutants Synergy in ESR1 Mutant Model Mechanisms of Resistance ESR1 Mutations Stimulate PR Require PR for Growth ** **** 16 60 shGFP shPR 12 40 8 20 **** 4 ** Veh Ful Ona Ona + 0 Ful WT ER ER Y537S Patient-derived ER+,PR+ / ESR1mutant hom MCF7 WT and MCF7 ESR1:Y537S were organoids (WHIM20), stimulated with stimulated with estradiol and treated with T47D cells stably transduced with ESR WT estradiol (E2) and treated with onapristone vehicle (shGFP) or treatment (shPR) for 5 and point mutants and were grown in CSS (100nM), fulvestrant (100nm), or both for 5 days medium for 8 days, followed by western blot days 1 ESR1 Mut: Bartels, Mod Path, 2018; Lopez-Knowles, BJC, 2018 2 MAPK: Razavi, Cancer Cell, 2018; de Leeuw, Clin Cancer Res, 2018 39 Nasdaq: CNTX 3 PR Activity: Lopez-Knowles, BJC, 2018; Li, Cell Reports, 2013 Avg number mammospheres Number of Organoids
Rationale for ONA-XR Onapristone Clinical Experience Prior Treatments Antiprogestin Stage Patients (n) Clinical Indication Biomarker Data Reference Median (Range) 56% ORR, 17.5-month DoR Onapristone IR Robertson Breast Cancer Phase 2 19 Hormone naïve 67% CBR Locally Advanced or Metastatic (100mg QD) 1999 14.0 month PFS 10% ORR Onapristone IR Breast Cancer Phase 2 101 1 (1-2) 48% CBR Jonat 2002 Metastatic (100mg QD) 4.0 month PFS Onapristone XR *57% DCR Granulosa Cell Tumor of Ovary Phase 2 14 4 (2-17) PR+ Ongoing Metastatic (50mg BID) *21% 6-month PFS ONA-XR (10-50 mg) Onapristone IR 2.8 month PFS Castrate Resistant Prostate Cancer (10 - 50mg BID) Phase 1b/2 36 2 (1-4) PR+ Jayaram 2017 Active progression on Abiraterone ±Abiraterone ONA-XR (50 mg) + Abiraterone 4.4 month PFS Onapristone XR 25% DCR Breast Cancer Phase 1 20 9 (2-14) PR+ Cottu 2018 Metastatic (10 - 50mg BID) 15% 6-month PFS Onapristone XR 8% ORR Ovarian Cancer Phase 1 13 4 (2-10) PR+ Cottu 2018 Metastatic (10 - 50mg BID) 31% 6-month PFS * = immature data 40 Nasdaq: CNTX IR = immediate release; XR = extended releaseRationale for ONA-XR Onapristone Clinical Experience Prior Treatments Antiprogestin Stage Patients (n) Clinical Indication Biomarker Data Reference Median (Range) 56% ORR, 17.5-month DoR Onapristone IR Robertson Breast Cancer Phase 2 19 Hormone naïve 67% CBR Locally Advanced or Metastatic (100mg QD) 1999 14.0 month PFS 10% ORR Onapristone IR Breast Cancer Phase 2 101 1 (1-2) 48% CBR Jonat 2002 Metastatic (100mg QD) 4.0 month PFS Onapristone XR *57% DCR Granulosa Cell Tumor of Ovary Phase 2 14 4 (2-17) PR+ Ongoing Metastatic (50mg BID) *21% 6-month PFS ONA-XR (10-50 mg) Onapristone IR 2.8 month PFS Castrate Resistant Prostate Cancer (10 - 50mg BID) Phase 1b/2 36 2 (1-4) PR+ Jayaram 2017 Active progression on Abiraterone ±Abiraterone ONA-XR (50 mg) + Abiraterone 4.4 month PFS Onapristone XR 25% DCR Breast Cancer Phase 1 20 9 (2-14) PR+ Cottu 2018 Metastatic (10 - 50mg BID) 15% 6-month PFS Onapristone XR 8% ORR Ovarian Cancer Phase 1 13 4 (2-10) PR+ Cottu 2018 Metastatic (10 - 50mg BID) 31% 6-month PFS * = immature data 40 Nasdaq: CNTX IR = immediate release; XR = extended release
ONA-XR ONA-XR: Summary of Cumulative Serious Adverse Events* Overall 10mg BID 20mg BID 30mg BID 40mg BID 50mg BID 100mg QD (N=128) (N=16) (N=18) (N=15) (N=14) (N=47) (N=6) System Organ Class Preferred Term n (%) n (%) n (%) n (%) n (%) n (%)* n (%) Any Serious TEAE 34 (27) 7 (44) 7 (39) 6 (40) 3 (21) 9 (19) 1 (17) Ascites 2 (2) 0 0 0 1 (7) 1 (2) 0 Vomiting 2 (2) 0 1 (6) 1 (7) 0 0 0 Chest pain 2 (2) 0 1 (6) 0 1 (7) 0 0 Pneumonia 2 (2) 0 0 2 (13) 0 0 0 Femur fracture 2 (2) 0 0 1 (7) 0 1 (2) 0 Anemia 1 (1) 0 0 0 0 0 1 (17) Atrial fibrillation 1 (1) 0 0 0 0 1 (2) 0 Syncope 1 (1) 0 0 0 0 1 (2) 0 Retinal artery occlusion 1 (1) 0 1 (6) 0 0 0 0 Abdominal pain upper 1 (1) 1 (6) 0 0 0 0 0 Upper gastrointestinal hemorrhage 1 (1) 0 0 1 (7) 0 0 0 Volvulus 1 (1) 0 0 0 0 1 (2) 0 Death 1 (1) 0 0 0 0 1 (2) 0 Pyrexia 1 (1) 0 1 (6) 0 0 0 0 Portal vein thrombosis 1 (1) 1 (6) 0 0 0 0 0 Abdominal wall abscess 1 (1) 1 (6) 0 0 0 0 0 Post procedural cellulitis 1 (1) 0 0 0 1 (7) 0 0 Pyelonephritis 1 (1) 0 0 0 0 0 1 (17) Sepsis 1 (1) 0 0 0 0 1 (2) 0 Aspartate aminotransferase increased 1 (1) 1 (6) 0 0 0 0 0 Hypercalcaemia 1 (1) 0 0 0 1 (7) 0 0 Hyperkalaemia 1 (1) 0 0 0 1 (7) 0 0 Hyponatraemia 1 (1) 0 0 0 1 (7) 0 0 Hydronephrosis 1 (1) 0 0 0 0 0 1 (17) Urinary retention 1 (1) 0 0 1 (7) 0 0 0 41 * As of Dec 31, 2020 Nasdaq: CNTXONA-XR ONA-XR: Summary of Cumulative Serious Adverse Events* Overall 10mg BID 20mg BID 30mg BID 40mg BID 50mg BID 100mg QD (N=128) (N=16) (N=18) (N=15) (N=14) (N=47) (N=6) System Organ Class Preferred Term n (%) n (%) n (%) n (%) n (%) n (%)* n (%) Any Serious TEAE 34 (27) 7 (44) 7 (39) 6 (40) 3 (21) 9 (19) 1 (17) Ascites 2 (2) 0 0 0 1 (7) 1 (2) 0 Vomiting 2 (2) 0 1 (6) 1 (7) 0 0 0 Chest pain 2 (2) 0 1 (6) 0 1 (7) 0 0 Pneumonia 2 (2) 0 0 2 (13) 0 0 0 Femur fracture 2 (2) 0 0 1 (7) 0 1 (2) 0 Anemia 1 (1) 0 0 0 0 0 1 (17) Atrial fibrillation 1 (1) 0 0 0 0 1 (2) 0 Syncope 1 (1) 0 0 0 0 1 (2) 0 Retinal artery occlusion 1 (1) 0 1 (6) 0 0 0 0 Abdominal pain upper 1 (1) 1 (6) 0 0 0 0 0 Upper gastrointestinal hemorrhage 1 (1) 0 0 1 (7) 0 0 0 Volvulus 1 (1) 0 0 0 0 1 (2) 0 Death 1 (1) 0 0 0 0 1 (2) 0 Pyrexia 1 (1) 0 1 (6) 0 0 0 0 Portal vein thrombosis 1 (1) 1 (6) 0 0 0 0 0 Abdominal wall abscess 1 (1) 1 (6) 0 0 0 0 0 Post procedural cellulitis 1 (1) 0 0 0 1 (7) 0 0 Pyelonephritis 1 (1) 0 0 0 0 0 1 (17) Sepsis 1 (1) 0 0 0 0 1 (2) 0 Aspartate aminotransferase increased 1 (1) 1 (6) 0 0 0 0 0 Hypercalcaemia 1 (1) 0 0 0 1 (7) 0 0 Hyperkalaemia 1 (1) 0 0 0 1 (7) 0 0 Hyponatraemia 1 (1) 0 0 0 1 (7) 0 0 Hydronephrosis 1 (1) 0 0 0 0 0 1 (17) Urinary retention 1 (1) 0 0 1 (7) 0 0 0 41 * As of Dec 31, 2020 Nasdaq: CNTX
Breast Cancer 1 First Line Metastatic Breast Cancer Phase 1b/2 Adaptive Trial utilizing ctDNA for Selection of Patients Who Are at High Risk of Early Relapse First Line (1L) Dose Escalation and Expansion Standard of Care Patient Enrichment via ctDNA ® Ibrance ONA-XR + (palbociclib) ® Ibrance (palbociclib) + + Letrozole Letrozole Primary Endpoint: • ORR Secondary Endpoints • PFS, Safety Exploratory Endpoints Enroll patients with Monitor ctDNA Levels rising ctDNA • ctDNA, PR-related biomarkers Potential Whitespace Opportunity Within 1L HR+,HER2- mBCa 1 NCT04872608 42 Nasdaq: CNTXBreast Cancer 1 First Line Metastatic Breast Cancer Phase 1b/2 Adaptive Trial utilizing ctDNA for Selection of Patients Who Are at High Risk of Early Relapse First Line (1L) Dose Escalation and Expansion Standard of Care Patient Enrichment via ctDNA ® Ibrance ONA-XR + (palbociclib) ® Ibrance (palbociclib) + + Letrozole Letrozole Primary Endpoint: • ORR Secondary Endpoints • PFS, Safety Exploratory Endpoints Enroll patients with Monitor ctDNA Levels rising ctDNA • ctDNA, PR-related biomarkers Potential Whitespace Opportunity Within 1L HR+,HER2- mBCa 1 NCT04872608 42 Nasdaq: CNTX
Breast Cancer 1 Second / Third Line Metastatic Breast Cancer Phase 2 Trial Evaluating Complete Hormone Blockade in Women Who Progressed on Prior Therapy in the Metastatic Setting Endpoints: • Primary: ORR Stage 1 Stage 2 • Secondary: ctDNA, PFS, safety ONA-XR ONA-XR 2L / 3L + + ER+,PR+,HER2- Fulvestrant Fulvestrant Breast Cancer Total N = 22 Total N = 18 Subgroup Analysis Documented Tumor Progression • ESR1 and PIK3CA mutations • PR-related biomarkers Intended to Establish Combination Synergy After Failure of CDK4/6 and/or PI3Kα Inhibitors 1 NCT04738292 43 Nasdaq: CNTXBreast Cancer 1 Second / Third Line Metastatic Breast Cancer Phase 2 Trial Evaluating Complete Hormone Blockade in Women Who Progressed on Prior Therapy in the Metastatic Setting Endpoints: • Primary: ORR Stage 1 Stage 2 • Secondary: ctDNA, PFS, safety ONA-XR ONA-XR 2L / 3L + + ER+,PR+,HER2- Fulvestrant Fulvestrant Breast Cancer Total N = 22 Total N = 18 Subgroup Analysis Documented Tumor Progression • ESR1 and PIK3CA mutations • PR-related biomarkers Intended to Establish Combination Synergy After Failure of CDK4/6 and/or PI3Kα Inhibitors 1 NCT04738292 43 Nasdaq: CNTX
Breast Cancer Pharmacodynamic Studies Study Target Deliverables • Target engagement 1 Radiolabeled Progesterone • Confirmation of recommended 18 ( F-FFNP PET) Uptake in Tumors phase 2 dose (RP2D) • Drug distribution 2 Window of Opportunity • On-target drug effects in primary breast cancer Studies Seek to Confirm Target Engagement and On-target Drug Effects 1 2 NCT04738292; NCT04142892 44 Nasdaq: CNTX
Corporate Partnerships Worldwide Exclusive License to CMC Partnership and Out-licensing of Rights CDLN6 Antibody in Bispecific Format to ONA-XR in Greater China • Integral Molecular to design and optimize CLDN6 x • Tyligand designed and optimized a novel onapristone CD3 bispecific antibody manufacturing process • Context to fund all development and commercial • Tyligand received license to ONA-XR in Greater China activities • Integral received upfront payment and is eligible to receive future milestones and royalties Value-Creating Partnerships Mutually Beneficial Expands Pipeline Capital Efficient Economics 45 Nasdaq: CNTXCorporate Partnerships Worldwide Exclusive License to CMC Partnership and Out-licensing of Rights CDLN6 Antibody in Bispecific Format to ONA-XR in Greater China • Integral Molecular to design and optimize CLDN6 x • Tyligand designed and optimized a novel onapristone CD3 bispecific antibody manufacturing process • Context to fund all development and commercial • Tyligand received license to ONA-XR in Greater China activities • Integral received upfront payment and is eligible to receive future milestones and royalties Value-Creating Partnerships Mutually Beneficial Expands Pipeline Capital Efficient Economics 45 Nasdaq: CNTX